title: Two novel splice variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are coupregulated with SOX2 and OCT4 in esophageal squamous cell carcinoma.
abstract: Long noncoding RNAs (lncRNAs) have emerged as new regulators of stem cell pluripotency and tumorigenesis. The SOX2 gene, a master regulator of pluripotency, is embedded within the third intron of a lncRNA known as SOX2 overlapping transcript (SOX2OT). SOX2OT has been suspected to participate in regulation of SOX2 expression and/or other related processes; nevertheless, its potential involvement in tumor initiation and/or progression is unclear. Here, we have evaluated a possible correlation between expression patterns of SOX2OT and those of master regulators of pluripotency, SOX2 and OCT4, in esophageal squamous cell carcinoma (ESCC) tissue samples. We have also examined its potential function in the human embryonic carcinoma stem cell line, NTERA2 (NT2), which highly expresses SOX2OT, SOX2, and OCT4. Our data revealed a significant coupregulation of SOX2OT along with SOX2 and OCT4 in tumor samples, compared to the non-tumor tissues obtained from the margin of same tumors. We also identified two novel splice variants of SOX2OT (SOX2OT-S1 and SOX2OT-S2) which coupregulated with SOX2 and OCT4 in ESCCs. Suppressing SOX2OT variants caused a profound alteration in cell cycle distribution, including a 5.9 and 6.9 time increase in sub-G1 phase of cell cycle for SOX2OT-S1 and SOX2OT-S2, respectively. The expression of all variants was significantly diminished, upon the induction of neural differentiation in NT2 cells, suggesting their potential functional links to the undifferentiated state of the cells. Our data suggest a part for SOX2OT spliced variants in tumor initiation and/or progression as well as regulating pluripotent state of stem cells.
authors.affiliation: Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Shahryari
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Rafiee
authors.forename: Youssef
authors.initials: Y
authors.lastname: Fouani
authors.forename: Nasrin Alipour
authors.initials: NA
authors.lastname: Oliae
authors.forename: Nader Mansour
authors.initials: NM
authors.lastname: Samaei
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shafiee
authors.forename: Shahryar
authors.initials: S
authors.lastname: Semnani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Vasei
authors.forename: Seyed Javad
authors.initials: SJ
authors.lastname: Mowla
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D020033:Protein Isoforms; D034622:RNA Interference; D012326:RNA Splicing; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D020033:Protein Isoforms; D062085:RNA, Long Noncoding; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: ESCC; LncRNA; Novel spliced variants; SOX2; SOX2OT; Stem cell